1. Field of the Invention
The present invention relates to a process for the preparation of sintered barium sulfate which is suitable for the preparation of radiographic contrast agents. The invention also includes the barium sulfate obtained according to this process, which has an increased bulk density as compared to that of the starting material and whose aqueous suspensions have a greatly increased flowability, as well as the correspondingly improved radiographic contrast material produced from this sintered material.
2. Description of the Prior Art
Barium sulfate continues to be the most important radio-opaque component in radiographic contrast materials used for visualizing the gastrointestinal tract. Numerous new barium sulfate preparations and corresponding patents confirm the unsurpassed basic suitability of this radio-opaque compound.
For practical applications, barium sulfate preparations are desired which combine the highest radiation absorption with good flowability so that the preparations penetrate into all parts and folds of the body, and adequate shadow density is obtained even when the layer is thin.
German Offenlegungsschrift No. 2,703,600 of 8/3/78 (Fredi Fischer) is exemplary of the state of the art for generally applicable preparations. This patent discloses that barium sulfate, suitable for use as a radiographic contrast agent, should have a bulk density of at least 1.2 g/ml and preferably of 1.6 to 1.7 g/ml.
Radiographic contrast agents which are suitable for the double contrast visualization of the stomach and gastric mucosa must meet even stricter requirements in respect to density and flowability. Double contrast visualization is a method developed in recent years for detecting lesions of the gastric mucosa which usually represent the first stage of a carcinosis of the gastric wall (R. E. Miller and J. Skucas, Radiographic Contrast Agents, University Park Press 1977, pages 144-146). The prospects of treating stomach cancer can be improved dramatically through the early identification of such lesions. As is well known, advanced stomach cancer which can also be identified by conventional contrasting agents, has a very poor prognosis (I. Laufer et al, Diagnostic Radiology, Vol. 115, June 1975, pages 569-575).
In the double contrast visualization of the stomach or the gastric mucosa, for example, the stomach is filled tightly with carbon dioxide which is given off by carbonates administered to the stomach. A relatively small amount of a highly concentrated barium sulfate suspension of the lowest possible viscosity is now introduced. If the barium sulfate suspension is sufficiently flowable, it spreads over the extended gastric wall with all its recesses and fine structures, while the gas itself acts as a negative contrasting agent. A fine layer of barium sulfate is to form on the folds of the mucous membrane in a way that it becomes visible in the double contrast X-ray picture, provided the barium sulfate suspension is sufficiently concentrated. The higher the concentration of the barium sulfate suspension, the thinner are the layers which can be identified in the X-ray picture. The more flowable the suspension, the better is the penetration into the finest interstices and folds and the more differentiated are the structures which become visible (I. Laufer, Diagnostic Radiology, Vol. 117, December 1975, pages 513-518).
By using double contrast visualization, it was possible to improve by far the proportion of carcinomas found. Under optimum conditions, carcinomas of a few millimeters to only 1 millimeter in diameter can be identified. The highest possible concentration and, at the same time, very good flowability of the barium sulfate suspension used over a wide pH range, are thus the primary absolute requirement for good double contrast visualizations. The gastric juice, whose pH can fluctuate over a wide range, should not cause any flocculation of the contrasting agent. (R. E. Miller and J. Skucas, loc. cit.)
The double contrast visualization of the intestinal mucosa with which relatively slight typical changes in the mucosa relief, and therefore carcinoma in the early stages, can be diagnosed, is based on a similar principle.
Barium sulfate formulations suitable for the double contrast visualization of the stomach or the gastric mucosa should contain at least 200, and preferably 250 g, of barium sulfate per 100 ml. Formulations of the required high concentration which are adequately flowable can usually not be prepared from conventional commercially available precipitated barium sulfate powders conforming to the requirements of the pharmacopeia. This is so whether coarsely or very finely milled preparations are used for this purpose (cf., for example, W. B. James, British Journal of Radiology, 51, 1978, pages 1020-1022). Certain mineral barium sulfates from South Australia, for example, after being milled to particle sizes of about 1 to 30 .mu.m, produce highly concentrated suspensions of sufficient flowability. Unfortunately, such baryta generally do not satisfy the purity requirements of the pharmacopeias. They usually contain too high a concentration of heavy metals (R. E. Miller and J. Skucas, loc. cit.).
Therefore, an acute need exists for barium sulfate of high bulk density whose highly concentrated aqueous suspensions have good flowability.